Thiazolidinedione

	WikiDoc Resources for Thiazolidinedione
Articles
Most recent articles on Thiazolidinedione Most cited articles on Thiazolidinedione Review articles on Thiazolidinedione Articles on Thiazolidinedione in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Thiazolidinedione Images of Thiazolidinedione Photos of Thiazolidinedione Podcasts & MP3s on Thiazolidinedione Videos on Thiazolidinedione
Evidence Based Medicine
Cochrane Collaboration on Thiazolidinedione Bandolier on Thiazolidinedione TRIP on Thiazolidinedione
Clinical Trials
Ongoing Trials on Thiazolidinedione at Clinical Trials.gov Trial results on Thiazolidinedione Clinical Trials on Thiazolidinedione at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Thiazolidinedione NICE Guidance on Thiazolidinedione NHS PRODIGY Guidance FDA on Thiazolidinedione CDC on Thiazolidinedione
Books
Books on Thiazolidinedione
News
Thiazolidinedione in the news Be alerted to news on Thiazolidinedione News trends on Thiazolidinedione
Commentary
Blogs on Thiazolidinedione
Definitions
Definitions of Thiazolidinedione
Patient Resources / Community
Patient resources on Thiazolidinedione Discussion groups on Thiazolidinedione Patient Handouts on Thiazolidinedione Directions to Hospitals Treating Thiazolidinedione Risk calculators and risk factors for Thiazolidinedione
Healthcare Provider Resources
Symptoms of Thiazolidinedione Causes & Risk Factors for Thiazolidinedione Diagnostic studies for Thiazolidinedione Treatment of Thiazolidinedione
Continuing Medical Education (CME)
CME Programs on Thiazolidinedione
International
Thiazolidinedione en Espanol Thiazolidinedione en Francais
Business
Thiazolidinedione in the Marketplace Patents on Thiazolidinedione
Experimental / Informatics
List of terms related to Thiazolidinedione

Overview

The medication class of thiazolidinedione was introduced in the late 1990s as an adjunctive therapy for diabetes mellitus (type 2) and related diseases.

Mode of action

Thiazolidinediones or TZDs act by binding to PPARs (peroxisome proliferator-activated receptors), a group of receptor molecules inside the cell nucleus, specifically PPARγ (gamma). The normal ligands for these receptors are free fatty acids (FFAs) and eicosanoids. When activated, the receptor migrates to the DNA, activating transcription of a number of specific genes.

Genes upregulated by PPARγ can be found in the main article on peroxisome proliferator-activated receptors.

By activating PPARγ:

Insulin resistance is decreased
Adipocyte differentiation is modified
VEGF-induced angiogenesis is inhibited^[1]
Leptin levels decrease (leading to an increased appetite)
Levels of certain interleukins (e.g. IL-6) fall
Adiponectin levels rise

Members of the class

The chemical structure of thiazolidinedione

Chemically, the members of this class are derivatives of the parent compound thiazolidinedione, and include:

Rosiglitazone (Avandia)
Pioglitazone (Actos)
Troglitazone (Rezulin), which was withdrawn from the market due to an increased incidence of drug-induced hepatitis.

Experimental agents include MCC-555, a powerful antidiabetic agent and the early non-marketed thiazolidinedione ciglitazone.

Uses

The only approved use of the thiazolidinediones is in diabetes mellitus type 2.

It is being investigated experimentally in polycystic ovary syndrome (PCOS), non-alcoholic steatohepatitis (NASH),^[2] psoriasis,^[3] and other conditions.^[4]

Several forms of lipodystrophy cause insulin resistance, which has responded favorably to thiazolidinediones. There are some indications that thiazolidinediones provide some degree of the protection against initial stages of the breast carcinoma development.

Side effects and contraindications

The withdrawal of troglitazone has led to concerns of other thiazolidinediones increasing the risk of hepatitis. Guidelines now mention that for the first year of thiazolidinedione therapy, a two- or three-monthly check of liver enzymes is conducted to ascertain that no liver damage is occurring.

The main side effect of all thiazolidinediones is fluid retention, leading to edema, weight gain, and potentially aggravating heart failure. Therefore, thiazolidinediones should not be prescribed in patients with decreased ventricular function (NYHA grade III or IV heart failure).

Recent studies have shown there may be an increase risk of CHD with Rosiglitazone.^[5] However, the PROactive study has shown that pioglitazone dose not have this same risk.

Footnotes

↑ Panigrahy D, Singer S, Shen LQ; et al. (2002). "PPARgamma ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis". J. Clin. Invest. 110 (7): 923–32. PMID 12370270.
↑ Belfort R et. al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355(22): 2297-307. PMID 17135584 Clinical trial info
↑ Krentz AJ, Friedmann PS. Type 2 diabetes, psoriasis and thiazolidinediones. Int J Clin Pract 2006;60:362-3. PMID 16494655.
↑ Clinical Trials for Rosiglitazone - from ClinicalTrials.gov, a service of the U.S. National Institutes of Health
↑ "Avandia to Carry Stronger Heart Failure Warning - Forbes.com". Retrieved 2007-08-15.

Template:Oral hypoglycemics de:Insulin-Sensitizer

Template:WikiDoc Sources

[1] Panigrahy D, Singer S, Shen LQ; et al. (2002). "PPARgamma ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis". J. Clin. Invest. 110 (7): 923–32. PMID 12370270.

[NASH-2] Belfort R et. al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355(22): 2297-307. PMID 17135584 Clinical trial info

[3] Krentz AJ, Friedmann PS. Type 2 diabetes, psoriasis and thiazolidinediones. Int J Clin Pract 2006;60:362-3. PMID 16494655.

[trials-4] Clinical Trials for Rosiglitazone - from ClinicalTrials.gov, a service of the U.S. National Institutes of Health

[5] "Avandia to Carry Stronger Heart Failure Warning - Forbes.com". Retrieved 2007-08-15.

[1]

[2]

[3]

[4]

[5]